Fat absorption is impaired in the normal human newborn, whether breast or bottle fed. The competency of fat digestion is inversely correlated with postnatal age and birth weight. This observed incompetence of fat digestion may compromise nutrition and, therefore, growth at a critical phase of development. Although the cause of fat malabsorption is incompletely understood, transient reduction in prandial intraluminal bile salt concentrations plays a key role. Multiple components of the enterohepatic circulation of bile salts are impaired at birth including hepatic synthesis, hepatic uptake and intestinal transport; with increasing postnatal age, all these processes mature in an asynchronous manner. Failure to develop a competent enterohepatic circulation of bile salts produces life-threatening diarrhea and serious impairment of growth and development. The present proposal is designed to describe the ontogenesis of intestinal bile salt transport in the rat and guinea pig using an in vitro incubation technique, and to explore the mechanisms which modulate its development. Functional changes will be correlated with the rate of de novo cell proliferation and protein synthesis indirectly by studying two key enzymes in polyamine metabolism, diamine oxidase and ornithine decarboxylase. Changes in microvillus membrane lipid composition and microviscosity will be studied to explore their role in the expression of ileal active bile salt transport. Our studies will examine the roles of hormonal and dietary factors in the regulation of development of intestinal bile salt transport. Specifically, glucocorticoids will be examined to determine whether precocious postnatal increases in serum corticoid concentrations will produce premature development or if adrenalectomy alters the developmental sequence. Future studies will examine the role of thyroxine and dietary components. This work should result in a concise understanding of the time sequence, biochemical correlates and modulating influences of the development of the ileal bile salt transport system.